# Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

**Authors:** Stefano Marletta, Nicola Fusco, Enrico Munari, Claudio Luchini, Alessia Cimadamore, Matteo Brunelli, Giulia Querzoli, Maurizio Martini, Elena Vigliar, Romano Colombari, Ilaria Girolami, Fabio Pagni, Albino Eccher

PMC · DOI: 10.3390/jpm12071073 · 2022-06-29

## TL;DR

This paper reviews how PD-L1 testing is used in cancer treatment decisions, highlighting current guidelines and areas needing more research.

## Contribution

The paper provides an updated overview of PD-L1 assessment methods and scoring systems across different cancer types.

## Key findings

- TPS, IC, and CPS scoring systems are recommended for lung, breast, and head and neck cancers.
- Guidelines for PD-L1 testing in gastroenteric neoplasms remain limited.
- Harmonization of PD-L1 assessment protocols is needed for better cancer treatment targeting.

## Abstract

Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable.

## Linked entities

- **Proteins:** CD274 (CD274 molecule), PDCD1 (programmed cell death 1)
- **Diseases:** cancer (MONDO:0004992), lung cancer (MONDO:0005138), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, PDCD1LG2 (programmed cell death 1 ligand 2) [NCBI Gene 80380] {aka B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}
- **Diseases:** UC (MESH:D014523), adenocarcinoma (MESH:D000230), TNBC (MESH:D064726), RCC (MESH:D002292), MSI (MESH:D053842), T-cell disorder (MESH:C536780), CPS (MESH:D053632), undifferentiated carcinoma (MESH:D002277), intestinal cancers (MESH:D007414), Inflammatory (MESH:D007249), lymphoid neoplasms (MESH:D008223), esophageal-gastric tumors (MESH:D013274), DLBCL (MESH:D016403), papillary carcinoma (MESH:D002291), Head and Neck Cancer (MESH:D006258), pancreatic ductal adenocarcinoma (MESH:D021441), metastatic disease (MESH:D000092182), squamous cell carcinoma (MESH:D002294), Breast Cancer (MESH:D001943), HNSCC (MESH:D000077195), Hematological Disorders (MESH:D006402), TC (OMIM:275350), lung adenocarcinoma (MESH:D000077192), dysplasia (MESH:D015792), CHL (MESH:D006689), Kidney Cancer (MESH:D007680), carcinoma in situ (MESH:D002278), hematological neoplasms (MESH:D019337), NSCLC (MESH:D002289), GE cancer (MESH:D009369), SCLC (MESH:D055752), gastro-esophageal (MESH:D005764), non-Hodgkin lymphoma (MESH:D008228), Colon and pancreas cancer (MESH:D015179), Melanoma (MESH:D008545), primary mediastinal large B cell lymphomas (MESH:D016393), ALCL (MESH:D017728), junction (MESH:D020511), gastroenteric neoplasms (MESH:D005759), Gastrointestinal Cancers (MESH:D005770), T-cell lymphomas (MESH:D016399), Lung Cancer (MESH:D008175), tumors of the esophagus (MESH:D004938), esophageal malignancies (MESH:D004941)
- **Chemicals:** paraffin (MESH:D010232), Durvalumab (MESH:C000613593), TC (MESH:D013667), fluorouracil (MESH:D005472), cisplatin (MESH:D002945), Atezolizumab (MESH:C000594389), eosin (MESH:D004801), Ipilimumab (MESH:D000074324), axitinib (MESH:D000077784), platinum (MESH:D010984), Nivolumab (MESH:D000077594), Hematoxylin (MESH:D006416), Keytruda (MESH:C582435), sunitinib (MESH:D000077210), Avelumab (MESH:C000609138), formalin (MESH:D005557), SP-142 (-)
- **Species:** human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** 28-8 — Oryctolagus cuniculus (Rabbit), Transformed cell line (CVCL_6E94), -426 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_DP95), SP263 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_B6L0), 22C3 — Mus musculus (Mouse), Conditionally immortalized cell line (CVCL_F277)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9321150/full.md

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Source: https://tomesphere.com/paper/PMC9321150